Synbiotics: Combination delivery of prebiotics and probiotics Sri Bagavathi Perumal RB, Santhosh Hariprakash, A. Liyana Sherin, Harinarayana Ankamreddy, Vaidyanathan Vinoth Kumar, Mohammad Tanvir Sarwar, Vinothkannan Ravichandran, Durga Mohan, Satish Kumar Rajasekharan Advances in Probiotic Delivery Systems Strategies for Enhanced Viability Targeted Delivery and Efficacy, 2025
Foxi3GFP and Foxi3CreER mice allow identification and lineage labeling of pharyngeal arch ectoderm and endoderm, and tooth and hair placodes Harinarayana Ankamreddy, Ankita Thawani, Onur Birol, Hongyuan Zhang, Andrew K. Groves Developmental Dynamics, 2023 BackgroundFOXI3 is a forkhead family transcription factor that is expressed in the progenitors of craniofacial placodes, epidermal placodes, and the ectoderm and endoderm of the pharyngeal arch region. Loss of Foxi3 in mice and pathogenic Foxi3 variants in dogs and humans cause a variety of craniofacial defects including absence of the inner ear, severe truncations of the jaw, loss or reduction in external and middle ear structures, and defects in teeth and hair.ResultsTo allow for the identification, isolation, and lineage tracing of Foxi3‐expressing cells in developing mice, we targeted the Foxi3 locus to create Foxi3GFP and Foxi3CreER mice. We show that Foxi3GFP mice faithfully recapitulate the expression pattern of Foxi3 mRNA at all ages examined, and Foxi3CreER mice can trace the derivatives of pharyngeal arch ectoderm and endoderm, the pharyngeal pouches and clefts that separate each arch, and the derivatives of hair and tooth placodes.ConclusionsFoxi3GFP and Foxi3CreER mice are new tools that will be of use in identifying and manipulating pharyngeal arch ectoderm and endoderm and hair and tooth placodes.
FOXI3 pathogenic variants cause one form of craniofacial microsomia Ke Mao, Christelle Borel, Muhammad Ansar, Angad Jolly, Periklis Makrythanasis, Christine Froehlich, Justyna Iwaszkiewicz, Bingqing Wang, Xiaopeng Xu, Qiang Li, Xavier Blanc, Hao Zhu, Qi Chen, Fujun Jin, Harinarayana Ankamreddy, Sunita Singh, Hongyuan Zhang, Xiaogang Wang, Peiwei Chen, Emmanuelle Ranza, Sohail Aziz Paracha, Syed Fahim Shah, Valentina Guida, Francesca Piceci-Sparascio, Daniela Melis, Bruno Dallapiccola, Maria Cristina Digilio, Antonio Novelli, Monia Magliozzi, Maria Teresa Fadda, Haley Streff, Keren Machol, Richard A. Lewis, Vincent Zoete, Gabriella Maria Squeo, Paolo Prontera, Giorgia Mancano, Giulia Gori, Milena Mariani, Angelo Selicorni, Stavroula Psoni, Helen Fryssira, Sofia Douzgou, Sandrine Marlin, Saskia Biskup, Alessandro De Luca, Giuseppe Merla, Shouqin Zhao, Timothy C. Cox, Andrew K. Groves, James R. Lupski, Qingguo Zhang, Yong-Biao Zhang, Stylianos E. Antonarakis Nature Communications, 2023 Craniofacial microsomia (CFM; also known as Goldenhar syndrome), is a craniofacial developmental disorder of variable expressivity and severity with a recognizable set of abnormalities. These birth defects are associated with structures derived from the first and second pharyngeal arches, can occur unilaterally and include ear dysplasia, microtia, preauricular tags and pits, facial asymmetry and other malformations. The inheritance pattern is controversial, and the molecular etiology of this syndrome is largely unknown. A total of 670 patients belonging to unrelated pedigrees with European and Chinese ancestry with CFM, are investigated. We identify 18 likely pathogenic variants in 21 probands (3.1%) in FOXI3. Biochemical experiments on transcriptional activity and subcellular localization of the likely pathogenic FOXI3 variants, and knock-in mouse studies strongly support the involvement of FOXI3 in CFM. Our findings indicate autosomal dominant inheritance with reduced penetrance, and/or autosomal recessive inheritance. The phenotypic expression of the FOXI3 variants is variable. The penetrance of the likely pathogenic variants in the seemingly dominant form is reduced, since a considerable number of such variants in affected individuals were inherited from non-affected parents. Here we provide suggestive evidence that common variation in the FOXI3 allele in trans with the pathogenic variant could modify the phenotypic severity and accounts for the incomplete penetrance.
The Foxi3 transcription factor is necessary for the fate restriction of placodal lineages at the neural plate border Ankita Thawani, Helen R. Maunsell, Hongyuan Zhang, Harinarayana Ankamreddy, Andrew K. Groves Development Cambridge, 2023 The Foxi3 transcription factor, expressed in the neural plate border at the end of gastrulation, is necessary for the formation of posterior placodes and is thus important for ectodermal patterning. We have created two knock-in mouse lines expressing GFP or a tamoxifen-inducible Cre recombinase to show that Foxi3 is one of the earliest genes to label the border between the neural tube and epidermis, and that Foxi3-expressing neural plate border progenitors contribute primarily to cranial placodes and epidermis from the onset of expression, but not to the neural crest or neural tube lineages. By simultaneously knocking out Foxi3 in neural plate border cells and following their fates, we show that neural plate border cells lacking Foxi3 contribute to all four lineages of the ectoderm – placodes, epidermis, crest and neural tube. We contrast Foxi3 with another neural plate border transcription factor, Zic5, the progenitors of which initially contribute broadly to all germ layers until gastrulation and gradually become restricted to the neural crest lineage and dorsal neural tube cells. Our study demonstrates that Foxi3 uniquely acts early at the neural plate border to restrict progenitors to a placodal and epidermal fate.
Uncovering the secreted signals and transcription factors regulating the development of mammalian middle ear ossicles Harinarayana Ankamreddy, Jinwoong Bok, Andrew K. Groves Developmental Dynamics, 2020 The mammalian middle ear comprises a chain of ossicles, the malleus, incus, and stapes that act as an impedance matching device during the transmission of sound from the tympanic membrane to the inner ear. These ossicles are derived from cranial neural crest cells that undergo endochondral ossification and subsequently differentiate into their final functional forms. Defects that occur during middle ear development can result in conductive hearing loss. In this review, we summarize studies describing the crucial roles played by signaling molecules such as sonic hedgehog, bone morphogenetic proteins, fibroblast growth factors, notch ligands, and chemokines during the differentiation of neural crest into the middle ear ossicles. In addition to these cell‐extrinsic signals, we also discuss studies on the function of transcription factor genes such as Foxi3, Tbx1, Bapx1, Pou3f4, and Gsc in regulating the development and morphology of the middle ear ossicles.
CXCL12 is required for stirrup-shaped stapes formation during mammalian middle ear development Harinarayana Ankamreddy, Heiyeun Koo, Young Jae Lee, Jinwoong Bok Developmental Dynamics, 2020 The mammalian middle ear comprises a chain of three ossicles—the malleus, incus, and stapes—each of which has a unique morphology for efficiently transmitting sound information. In particular, the stapes, which is attached to the inner ear, is stirrup‐shaped with a head and base connected by two crural arches, forming the stapedial foramen, through which the stapedial artery passes. However, how the stapes acquires this critical stirrup shape for association with the stapedial artery during development is not clear.
Region-specific endodermal signals direct neural crest cells to form the three middle ear ossicles Harinarayana Ankamreddy, Hyehyun Min, Jae Yoon Kim, Xiao Yang, Eui-Sic Cho, Un-Kyung Kim, Jinwoong Bok Development Cambridge, 2019 Defects in the middle ear ossicles - malleus, incus, and stapes - can lead to conductive hearing loss. During development, neural crest cells (NCCs) migrate from the dorsal hindbrain to specific locations in pharyngeal arch (PA) 1 and 2, to form the malleus-incus and stapes, respectively. It is unclear how migratory NCCs reach their proper destination in PA and initiate mesenchymal condensation to form specific ossicles. We show that secreted molecules sonic hedgehog (SHH) and bone morphogenetic protein 4 (BMP4) emanating from the pharyngeal endoderm are important in instructing regional-specific NCC condensation to form malleus-incus and stapes, respectively. Tissue-specific knockout of Shh in the pharyngeal endoderm or Smoothened (a transducer of SHH signaling) in NCCs causes the loss of malleus-incus condensation in PA1 but only affects the maintenance of stapes condensation in PA2. By contrast, knockout of Bmp4 in the pharyngeal endoderm or Smad4 (a transducer of TGF-β/BMP signaling) in the NCCs disrupts NCC migration into the stapes region in PA2, affecting the stapes formation. These results indicate that regional-specific endodermal signals direct formation of specific middle ear ossicles.
Temporal and spatial expression patterns of hedgehog receptors in the developing inner and middle ear Jeong-Oh Shin, Harinarayana Ankamreddy, Naga Mahesh Jakka, Seokwon Lee, Un-Kyung Kim, Jinwoong Bok International Journal of Developmental Biology, 2017 The mammalian inner ear is a complex organ responsible for balance and hearing. Sonic hedgehog (Shh), a member of the Hedgehog (Hh) family of secreted proteins, has been shown to play important roles in several aspects of inner ear development, including dorsoventral axial specification, cochlear elongation, tonotopic patterning, and hair cell differentiation. Hh proteins initiate a downstream signaling cascade by binding to the Patched 1 (Ptch1) receptor. Recent studies have revealed that other types of co-receptors can also mediate Hh signaling, including growth arrest-specific 1 (Gas1), cell-adhesion molecules-related/down-regulated by oncogenes (Cdon), and biregional Cdon binding protein (Boc). However, little is known about the role of these Hh co-receptors in inner ear development. In this study, we examined the expression patterns of Gas1, Cdon, and Boc, as well as that of Ptch1, in the developing mouse inner ear from otocyst (embryonic day (E) 9.5) until birth and in the developing middle ear at E15.5. Ptch1, a readout of Hh signaling, was expressed in a graded pattern in response to Shh signaling throughout development. Expression patterns of Gas1, Cdon, and Boc differed from that of Ptch1, and each Hh co-receptor was expressed in specific cells and domains in the developing inner and middle ear. These unique and differential expression patterns of Hh co-receptors suggest their roles in mediating various time- and space-specific functions of Shh during ear development.
Pannexin 3 is required for normal progression of skeletal development in vertebrates Se‐Kyung Oh, Jeong‐Oh Shin, Jeong‐In Baek, Jinwook Lee, Jae Woong Bae, Harinarayana Ankamerddy, Myoung‐Jin Kim, Tae‐Lin Huh, Zae‐Young Ryoo, Un‐Kyung Kim, Jinwoong Bok, Kyu‐Yup Lee FASEB Journal, 2015 The vertebrate skeletal system has various functions, including support, movement, protection, and the production of blood cells. The development of cartilage and bones, the core components of the skeletal system, is mediated by systematic inter‐ and intracellular communication among multiple signaling pathways in differentiating progenitors and the surrounding tissues. Recently, Pannexin (Panx) 3 has been shown to play important roles in bone development in vitro by mediating multiple signaling pathways, although its roles in vivo have not been explored. In this study, we generated and analyzed Panx3 knockout mice and examined the skeletal phenotypes of panx3 morphant zebrafish. Panx3‐/‐ embryos exhibited delays in hypertrophic chondrocyte differentiation and osteoblast differentiation as well as the initiation of mineralization, resulting in shortened long bones in adulthood. The abnormal progression of hypertrophic chondrogenesis appeared to be associated with the sustained proliferation of chondrocytes, which resulted from increased intracellular cAMP levels. Similarly, osteoblast differentiation and mineralization were delayed in panx3 morphant zebrafish. Taken together, our results provide evidence of the crucial roles of Panx3 in vertebrate skeletal development in vivo.—Oh, S.‐K., Shin, J.‐O., Baek, J.‐I., Lee, J., Bae, J. W., Ankamerddy, H., Kim, M.‐J., Huh, T.‐L., Ryoo, Z.‐Y., Kim, U.‐K., Bok, J., Lee, K.‐Y. Pannexin 3 is required for normal progression of skeletal development in vertebrates. FASEB J. 29, 4473‐4484 (2015). www.fasebj.org
Conserved role of Sonic Hedgehog in tonotopic organization of the avian basilar papilla and mammalian cochlea Eun Jin Son, Ji-Hyun Ma, Harinarayana Ankamreddy, Jeong-Oh Shin, Jae Young Choi, Doris K. Wu, Jinwoong Bok Proceedings of the National Academy of Sciences of the United States of America, 2015 Significance Sound frequency discrimination is crucial for daily activities throughout the animal kingdom. This process begins at the auditory peripheral organ known as the organ of Corti in mammals and basilar papilla in birds. This frequency tuning is facilitated by specific anatomical and physiological properties, including gradual changes in the shape of the mechanosensory hair cells and the total number of stereocilia per hair cell along the cochlea. Unlike in birds, the molecular mechanism(s) that establishes this tonotopic organization is not known in mammals. In this study, we provide in vivo evidence that Sonic Hedgehog signaling mediates regional identity of the developing cochlea in both mammals and birds, and this regional identity prefigures the tonotopic organization in the basilar papilla.
Microbial methanotrophy: Methane capture to biomanufacturing of platform chemicals and fuels TB Madavi, S Chauhan, V Madathil, M Sankaranarayanan, B Navina, ... Next Energy 8, 100251 , 2025 2025.0 Citations: 5
Foxi3 GFP and Foxi3 CreER mice allow identification and lineage labeling of pharyngeal arch ectoderm and endoderm, and tooth and hair placodes H Ankamreddy, A Thawani, O Birol, H Zhang, AK Groves Developmental Dynamics 252 (12), 1462-1470 , 2023 2023.0 Citations: 6
The Foxi3 transcription factor is necessary for the fate restriction of placodal lineages at the neural plate border A Thawani, HR Maunsell, H Zhang, H Ankamreddy, AK Groves Development 150 (19), dev202047 , 2023 2023.0 Citations: 7
FOXI3 pathogenic variants cause one form of craniofacial microsomia K Mao, C Borel, M Ansar, A Jolly, P Makrythanasis, C Froehlich, ... Nature communications 14 (1), 2026 , 2023 2023.0 Citations: 39
Uncovering the secreted signals and transcription factors regulating the development of mammalian middle ear ossicles H Ankamreddy, J Bok, AK Groves Developmental Dynamics 249 (12), 1410-1424 , 2020 2020.0 Citations: 17
CXCL12 is required for stirrup‐shaped stapes formation during mammalian middle ear development H Ankamreddy, H Koo, YJ Lee, J Bok Developmental Dynamics 249 (9), 1117-1126 , 2020 2020.0 Citations: 5
Follistatin, a possible downstream mediator of Sonic Hedgehog signaling is important for low-frequency hearing H Koo, MA Kim, H Min, JY Hwang, M Prajapati, JO Shin, JH Ma, ... 한국실험동물학회 학술발표대회 논문집, 132-132 , 2020 2020.0
Region-specific endodermal signals direct neural crest cells to form the three middle ear ossicles H Ankamreddy, H Min, JY Kim, X Yang, ES Cho, UK Kim, J Bok Development 146 (2), dev167965 , 2019 2019.0 Citations: 24
Temporal and spatial expression patterns of Hedgehog receptors in the developing inner and middle ear JO Shin, H Ankamreddy, NM Jakka, S Lee, UK Kim, J Bok Int J Dev Biol 61 (8-9), 557-563 , 2017 2017.0 Citations: 10
Pannexin 3 is required for normal progression of skeletal development in vertebrates SK Oh, JO Shin, JI Baek, J Lee, JW Bae, H Ankamerddy, MJ Kim, TL Huh, ... The FASEB Journal 29 (11), 4473-4484 , 2015 2015.0 Citations: 37
Conserved role of Sonic Hedgehog in tonotopic organization of the avian basilar papilla and mammalian cochlea EJ Son, JH Ma, H Ankamreddy, JO Shin, JY Choi, DK Wu, J Bok Proceedings of the National Academy of Sciences 112 (12), 3746-3751 , 2015 2015.0 Citations: 60
Pax3 function is required specifically for inner ear structures with melanogenic fates HK Kim, H Ankamreddy, DJ Lee, KA Kong, HW Ko, MH Kim, J Bok Biochemical and biophysical research communications 445 (3), 608-614 , 2014 2014.0 Citations: 32
Roles of hedgehog, bone morphogenetic protein 4 and CXCL12 signaling on middle ear development A Harinarayana
Temporal requirement of TGF-beta and Hedgehog signalling during middle ear ossicle formation XY Harinarayana Ankamreddy, ES Cho, J Bok
Role of Hedgehog and TGF-β signaling in middle ear development H Ankamreddy, D Han, HK Kim, X Yang, ES Cho, J Bok
MOST CITED SCHOLAR PUBLICATIONS
Conserved role of Sonic Hedgehog in tonotopic organization of the avian basilar papilla and mammalian cochlea EJ Son, JH Ma, H Ankamreddy, JO Shin, JY Choi, DK Wu, J Bok Proceedings of the National Academy of Sciences 112 (12), 3746-3751 , 2015 2015.0 Citations: 60
FOXI3 pathogenic variants cause one form of craniofacial microsomia K Mao, C Borel, M Ansar, A Jolly, P Makrythanasis, C Froehlich, ... Nature communications 14 (1), 2026 , 2023 2023.0 Citations: 39
Pannexin 3 is required for normal progression of skeletal development in vertebrates SK Oh, JO Shin, JI Baek, J Lee, JW Bae, H Ankamerddy, MJ Kim, TL Huh, ... The FASEB Journal 29 (11), 4473-4484 , 2015 2015.0 Citations: 37
Pax3 function is required specifically for inner ear structures with melanogenic fates HK Kim, H Ankamreddy, DJ Lee, KA Kong, HW Ko, MH Kim, J Bok Biochemical and biophysical research communications 445 (3), 608-614 , 2014 2014.0 Citations: 32
Region-specific endodermal signals direct neural crest cells to form the three middle ear ossicles H Ankamreddy, H Min, JY Kim, X Yang, ES Cho, UK Kim, J Bok Development 146 (2), dev167965 , 2019 2019.0 Citations: 24
Uncovering the secreted signals and transcription factors regulating the development of mammalian middle ear ossicles H Ankamreddy, J Bok, AK Groves Developmental Dynamics 249 (12), 1410-1424 , 2020 2020.0 Citations: 17
Temporal and spatial expression patterns of Hedgehog receptors in the developing inner and middle ear JO Shin, H Ankamreddy, NM Jakka, S Lee, UK Kim, J Bok Int J Dev Biol 61 (8-9), 557-563 , 2017 2017.0 Citations: 10
The Foxi3 transcription factor is necessary for the fate restriction of placodal lineages at the neural plate border A Thawani, HR Maunsell, H Zhang, H Ankamreddy, AK Groves Development 150 (19), dev202047 , 2023 2023.0 Citations: 7
Foxi3 GFP and Foxi3 CreER mice allow identification and lineage labeling of pharyngeal arch ectoderm and endoderm, and tooth and hair placodes H Ankamreddy, A Thawani, O Birol, H Zhang, AK Groves Developmental Dynamics 252 (12), 1462-1470 , 2023 2023.0 Citations: 6
Microbial methanotrophy: Methane capture to biomanufacturing of platform chemicals and fuels TB Madavi, S Chauhan, V Madathil, M Sankaranarayanan, B Navina, ... Next Energy 8, 100251 , 2025 2025.0 Citations: 5
CXCL12 is required for stirrup‐shaped stapes formation during mammalian middle ear development H Ankamreddy, H Koo, YJ Lee, J Bok Developmental Dynamics 249 (9), 1117-1126 , 2020 2020.0 Citations: 5
Follistatin, a possible downstream mediator of Sonic Hedgehog signaling is important for low-frequency hearing H Koo, MA Kim, H Min, JY Hwang, M Prajapati, JO Shin, JH Ma, ... 한국실험동물학회 학술발표대회 논문집, 132-132 , 2020 2020.0
Roles of hedgehog, bone morphogenetic protein 4 and CXCL12 signaling on middle ear development A Harinarayana
Temporal requirement of TGF-beta and Hedgehog signalling during middle ear ossicle formation XY Harinarayana Ankamreddy, ES Cho, J Bok
Role of Hedgehog and TGF-β signaling in middle ear development H Ankamreddy, D Han, HK Kim, X Yang, ES Cho, J Bok
