An Eya1-Notch axis specifies bipotential epibranchial differentiation in mammalian craniofacial morphogenesis

Haoran Zhang; Li Wang; Elaine Yee Man Wong; Sze Lan Tsang; Pin Xian Xu; Urban Lendahl; Mai Har Sham

doi:10.7554/eLife.30126

An Eya1-Notch axis specifies bipotential epibranchial differentiation in mammalian craniofacial morphogenesis

Haoran Zhang, Li Wang, Elaine Yee Man Wong, Sze Lan Tsang, Pin Xian Xu, Urban Lendahl, Mai Har Sham

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24 Scopus citations

Abstract

Craniofacial morphogenesis requires proper development of pharyngeal arches and epibranchial placodes. We show that the epibranchial placodes, in addition to giving rise to cranial sensory neurons, generate a novel lineage-related non-neuronal cell population for mouse pharyngeal arch development. Eya1 is essential for the development of epibranchial placodes and proximal pharyngeal arches. We identify an Eya1-Notch regulatory axis that specifies both the neuronal and non-neuronal commitment of the epibranchial placode, where Notch acts downstream of Eya1 and promotes the non-neuronal cell fate. Notch is regulated by the threonine phosphatase activity of Eya1. Eya1 dephosphorylates p-threonine-2122 of the Notch1 intracellular domain (Notch1 ICD), which increases the stability of Notch1 ICD and maintains Notch signaling activity in the non-neuronal epibranchial placodal cells. Our data unveil a more complex differentiation program in epibranchial placodes and an important role for the Eya1-Notch axis in craniofacial morphogenesis.

Original language	English
Article number	e30126
Journal	eLife
Volume	6
DOIs	https://doi.org/10.7554/eLife.30126
State	Published - 15 Nov 2017

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title = "An Eya1-Notch axis specifies bipotential epibranchial differentiation in mammalian craniofacial morphogenesis",

abstract = "Craniofacial morphogenesis requires proper development of pharyngeal arches and epibranchial placodes. We show that the epibranchial placodes, in addition to giving rise to cranial sensory neurons, generate a novel lineage-related non-neuronal cell population for mouse pharyngeal arch development. Eya1 is essential for the development of epibranchial placodes and proximal pharyngeal arches. We identify an Eya1-Notch regulatory axis that specifies both the neuronal and non-neuronal commitment of the epibranchial placode, where Notch acts downstream of Eya1 and promotes the non-neuronal cell fate. Notch is regulated by the threonine phosphatase activity of Eya1. Eya1 dephosphorylates p-threonine-2122 of the Notch1 intracellular domain (Notch1 ICD), which increases the stability of Notch1 ICD and maintains Notch signaling activity in the non-neuronal epibranchial placodal cells. Our data unveil a more complex differentiation program in epibranchial placodes and an important role for the Eya1-Notch axis in craniofacial morphogenesis.",

author = "Haoran Zhang and Li Wang and Wong, {Elaine Yee Man} and Tsang, {Sze Lan} and Xu, {Pin Xian} and Urban Lendahl and Sham, {Mai Har}",

note = "Funding Information: We would like to thank CC Hui for providing the Notch1 ICD plasmid; J Tanner, R Kok, DY Jin and CM Qian for technical advice. This work was supported by research grants from the Hong Kong Research Grants Council (RGC GRF 777411, RGC GRF 17113415) to MHS; and research grants from the Swedish Research Council (K2014-64X-20097-09-5), the Swedish Cancer Society (CAN 2016/271) and ICMC (Integrated Cardio Metabolic Center) to UL; and NIH RO1 grants (DK064640 and DC014718) to PXX. Publisher Copyright: {\textcopyright} Zhang et al.",

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AU - Wang, Li

AU - Wong, Elaine Yee Man

AU - Tsang, Sze Lan

AU - Xu, Pin Xian

AU - Lendahl, Urban

AU - Sham, Mai Har

N1 - Funding Information: We would like to thank CC Hui for providing the Notch1 ICD plasmid; J Tanner, R Kok, DY Jin and CM Qian for technical advice. This work was supported by research grants from the Hong Kong Research Grants Council (RGC GRF 777411, RGC GRF 17113415) to MHS; and research grants from the Swedish Research Council (K2014-64X-20097-09-5), the Swedish Cancer Society (CAN 2016/271) and ICMC (Integrated Cardio Metabolic Center) to UL; and NIH RO1 grants (DK064640 and DC014718) to PXX. Publisher Copyright: © Zhang et al.

PY - 2017/11/15

Y1 - 2017/11/15

N2 - Craniofacial morphogenesis requires proper development of pharyngeal arches and epibranchial placodes. We show that the epibranchial placodes, in addition to giving rise to cranial sensory neurons, generate a novel lineage-related non-neuronal cell population for mouse pharyngeal arch development. Eya1 is essential for the development of epibranchial placodes and proximal pharyngeal arches. We identify an Eya1-Notch regulatory axis that specifies both the neuronal and non-neuronal commitment of the epibranchial placode, where Notch acts downstream of Eya1 and promotes the non-neuronal cell fate. Notch is regulated by the threonine phosphatase activity of Eya1. Eya1 dephosphorylates p-threonine-2122 of the Notch1 intracellular domain (Notch1 ICD), which increases the stability of Notch1 ICD and maintains Notch signaling activity in the non-neuronal epibranchial placodal cells. Our data unveil a more complex differentiation program in epibranchial placodes and an important role for the Eya1-Notch axis in craniofacial morphogenesis.

AB - Craniofacial morphogenesis requires proper development of pharyngeal arches and epibranchial placodes. We show that the epibranchial placodes, in addition to giving rise to cranial sensory neurons, generate a novel lineage-related non-neuronal cell population for mouse pharyngeal arch development. Eya1 is essential for the development of epibranchial placodes and proximal pharyngeal arches. We identify an Eya1-Notch regulatory axis that specifies both the neuronal and non-neuronal commitment of the epibranchial placode, where Notch acts downstream of Eya1 and promotes the non-neuronal cell fate. Notch is regulated by the threonine phosphatase activity of Eya1. Eya1 dephosphorylates p-threonine-2122 of the Notch1 intracellular domain (Notch1 ICD), which increases the stability of Notch1 ICD and maintains Notch signaling activity in the non-neuronal epibranchial placodal cells. Our data unveil a more complex differentiation program in epibranchial placodes and an important role for the Eya1-Notch axis in craniofacial morphogenesis.

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An Eya1-Notch axis specifies bipotential epibranchial differentiation in mammalian craniofacial morphogenesis

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