Hey1 gene expression patterns during the development of branchial arches and facial prominences

Patrones de expresiòn del gen Hey1 durante el desarrollo de arcos branquiales y prominencias faciales

Objective. The present study aimed to describe in detail the expression patterns of the gene Hey1, an effector of the Notch pathway, during the development of branchial arches and facial prominences. Materials and methods. Fertilized chicken (Gallus gallus) eggs obtained from a local egg farm were incubated at 37.5 -38.5ºC with 70% relative humidity until the embryos reached Hamilton-Hamburger stages HH14 through HH25. Digoxigenin-UTP labeled probes Hey1 were generated from linearized plasmids with either T3 polimerase for in vitro transcription.  Whole-mount in situ hybridization was then performed. At least 3 replicates (n=3) were obtained for each stage. To confirm the results observed in whole embryos, sagittal and coronal cryosectioning was performed using a thickness of 10 µm. Results.  During developmental stages HH14 and HH18, Hey1 gene expression was localized to the endoderm of branchial pouches. Hey1 gene expression was also observed in the epithelium that covers the maxillary and mandibular prominences during developmental stages HH19 and HH21, as well as in the nasal epithelium between HH19 and HH25. Transcripts were also detected in the epithelium that covers the frontonasal prominence during stage HH21.Conclusions. These expression patterns suggest the participation of this component of the Notch signaling pathway in craniofacial morphogenesis, possibly establishing pharyngeal segmentation patterns during early stages and/or regulating cell proliferation and differentiation during the late stages of facial development.

1. Trainor PA. Molecular Blueprint for Craniofacial Morphogenesis and Development. Stem Cells in Craniofacial Development and Regeneration: John Wiley & Sons, Inc.; 2013. p. 1-29. https://doi.org/10.1002/9781118498026.ch1
3. Grevellec A, Tucker AS. The pharyngeal pouches and clefts: Development, evolution, structure and derivatives. Semin Cell Dev Biol . 2010;21(3):325-32. https://doi.org/10.1016/j.semcdb.2010.01.022
5. Parada C, Chai Y. Mandible and Tongue Development. Curr Top Dev Biol. 2015;115:31-58. . https://doi.org/10.1016/bs.ctdb.2015.07.023
7. Liu B, Rooker SM, Helms JA. Molecular control of facial morphology. Semin cell dev biol. 2010;21(3):309-13. https://doi.org/10.1016/j.semcdb.2009.09.002
9. Minoux M, Rijli FM. Molecular mechanisms of cranial neural crest cell migration and patterning in craniofacial development. Development. 2010;137(16):2605-21. https://doi.org/10.1242/dev.040048
11. Szabo-Rogers HL, Smithers LE, Yakob W, Liu KJ. New directions in craniofacial morphogenesis. Dev Biol. 2010;341(1):84-94. https://doi.org/10.1016/j.ydbio.2009.11.021
13. Talora C, Campese AF, Bellavia D, Felli MP, Vacca A, Gulino A, et al. Notch signaling and diseases: an evolutionary journey from a simple beginning to complex outcomes. Biochim Biophys Acta . 2008;1782(9):489-97. https://doi.org/10.1016/j.bbadis.2008.06.008
15. Schwanbeck R, Martini S, Bernoth K, Just U. The Notch signaling pathway: molecular basis of cell context dependency. Eur J Cell Biol. 2011;90(6-7):572-81. https://doi.org/10.1016/j.ejcb.2010.10.004
17. Iso T, Kedes L, Hamamori Y. HES and HERP families: multiple effectors of the Notch signaling pathway. J Cell Physiol. 2003;194(3):237-55. https://doi.org/10.1002/jcp.10208
19. Leimeister C, Externbrink A, Klamt B, Gessler M. Hey genes: a novel subfamily of hairy- and Enhancer of split related genes specifically expressed during mouse embryogenesis. Mech Develop. 1999;85(1-2):173-7. https://doi.org/10.1016/S0925-4773(99)00080-5
21. Ratie L, Ware M, Barloy-Hubler F, Rome H, Gicquel I, Dubourg C, et al. Novel genes upregulated when NOTCH signalling is disrupted during hypothalamic development. Neural Dev. 2013;8:25. https://doi.org/10.1186/1749-8104-8-25
23. Stefanovic S, Barnett P, van Duijvenboden K, Weber D, Gessler M, Christoffels VM. GATA-dependent regulatory switches establish atrioventricular canal specificity during heart development. Nat. Commun. 2014;5:3680. https://doi.org/10.1038/ncomms4680
25. Tateya T, Imayoshi I, Tateya I, Ito J, Kageyama R. Cooperative functions of Hes/Hey genes in auditory hair cell and supporting cell development. Dev Biol. 2011;352(2):329-40. https://doi.org/10.1016/j.ydbio.2011.01.038
27. Salie R, Kneissel M, Vukevic M, Zamurovic N, Kramer I, Evans G, et al. Ubiquitous overexpression of Hey1 transcription factor leads to osteopenia and chondrocyte hypertrophy in bone. Bone. 2010;46(3):680-94. https://doi.org/10.1016/j.bone.2009.10.022
29. Zuniga E, Stellabotte F, Crump JG. Jagged-Notch signaling ensures dorsal skeletal identity in the vertebrate face. Development. 2010;137(11):1843-52. https://doi.org/10.1242/dev.049056
31. Neves J, Parada C, Chamizo M, Giraldez F. Jagged 1 regulates the restriction of Sox2 expression in the developing chicken inner ear: a mechanism for sensory organ specification. Development. 2011;138(4):735-44. https://doi.org/10.1242/dev.060657
33. Rizzoti K, Lovell-Badge R. SOX3 activity during pharyngeal segmentation is required for craniofacial morphogenesis. Development. 2007;134(19):3437-48. https://doi.org/10.1242/dev.007906
35. Graham A, Okabe M, Quinlan R. The role of the endoderm in the development and evolution of the pharyngeal arches. J Anat. 2005;207(5):479-87. https://doi.org/10.1111/j.1469-7580.2005.00472.x
37. Szabo-Rogers HL, Geetha-Loganathan P, Nimmagadda S, Fu KK, Richman JM. FGF signals from the nasal pit are necessary for normal facial morphogenesis. Dev Biol. 2008;318(2):289-302. https://doi.org/10.1016/j.ydbio.2008.03.027
39. Tak HJ, Park TJ, Piao Z, Lee SH. Separate development of the maxilla and mandible is controlled by regional signaling of the maxillomandibular junction during avian development. Dev Dynam : an official publication of the American Association of Anatomists. 2017;246(1):28-40. https://doi.org/10.1002/dvdy.24465
41. Minkoff R, Kuntz AJ. Cell proliferation and cell density of mesenchyme in the maxillary process and adjacent regions during facial development in the chick embryo. J Embryol Exp Morph. 1978;46:65-74.
43. Dunlop LL, Hall BK. Relationships between cellular condensation, preosteoblast formation and epithelial-mesenchymal interactions in initiation of osteogenesis. Int J Dev Biol. 1995;39(2):357-71.
45. Ekanayake S, Hall BK. The in vivo and in vitro effects of bone morphogenetic protein-2 on the development of the chick mandible. Int J Dev Biol. 1997;41(1):67-81.
47. Merrill AE, Eames BF, Weston SJ, Heath T, Schneider RA. Mesenchyme-dependent BMP signaling directs the timing of mandibular osteogenesis. Development. 2008;135(7):1223-34. https://doi.org/10.1242/dev.015933
49. Oldershaw RA, Hardingham TE. Notch signaling during chondrogenesis of human bone marrow stem cells. Bone. 2010;46(2):286-93. https://doi.org/10.1016/j.bone.2009.04.242
51. Oldershaw RA, Tew SR, Russell AM, Meade K, Hawkins R, McKay TR, et al. Notch signaling through Jagged-1 is necessary to initiate chondrogenesis in human bone marrow stromal cells but must be switched off to complete chondrogenesis. Stem Cells. 2008;26(3):666-74. https://doi.org/10.1634/stemcells.2007-0806
53. Hu D, Marcucio RS. Unique organization of the frontonasal ectodermal zone in birds and mammals. Dev Biol. 2009;325(1):200-10. https://doi.org/10.1016/j.ydbio.2008.10.026
55. Abzhanov A, Cordero DR, Sen J, Tabin CJ, Helms JA. Cross-regulatory interactions between Fgf8 and Shh in the avian frontonasal prominence. Congenit Anom. 2007;47(4):136-48. https://doi.org/10.1111/j.1741-4520.2007.00162.x
57. Szabo-Rogers HL, Geetha-Loganathan P, Whiting CJ, Nimmagadda S, Fu K, Richman JM. Novel skeletogenic patterning roles for the olfactory pit. Development. 2009;136(2):219-29. https://doi.org/10.1242/dev.023978