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.
Highlights
Craniofacial morphogenesis depends on integration of signals from multiple cell types and is a complex morphogenetic process requiring, among other structures, the genesis of cranial placodes and pharyngeal arches
We examined the expression of the neural crest marker gene Crabp1 and confirmed that the migrating neural crest stream in the PA2 was reduced in the Eya1-/- embryos (Figure 1F and G)
The analysis of the Eya1-/- phenotype shows that the abnormal pharyngeal arch segmentation and proximal pharyngeal arches (PA) defects are likely the basis for the abnormal morphogenesis in Eya1-/embryos previously described (Xu et al, 1999)
Summary
Craniofacial morphogenesis depends on integration of signals from multiple cell types and is a complex morphogenetic process requiring, among other structures, the genesis of cranial placodes and pharyngeal arches. The cranial placodes are divided into the anterior (adenohypophyseal, olfactory and lens placodes), intermediate (trigeminal placode) and posterior placodes (otic, lateral line and epibranchial placodes) (Streit, 2007; Saint-Jeannet and Moody, 2014; Singh and Groves, 2016) (Figure 1A). It is believed that the principle function of the epibranchial placodes is to produce viscero-sensory neurons by delaminating cells that undergo neuronal differentiation (Narayanan and Narayanan, 1980). The pharyngeal arches (PA) are transient structures formed in the pharyngeal region of the early embryonic head and interactions of the pharyngeal epithelium, the endoderm, neural crest and mesenchyme give rise to facial, head and neck structures during development (Figure 1A). A key aspect of PA formation is the segmentation process, during which the pharyngeal endoderm
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