Abstract
The development of key structures within the mature vertebrate hindbrain requires the migration of neural crest (NC) cells and motor neurons to their appropriate target sites. Functional analyses in multiple species have revealed a requirement for the transcription factor gastrulation-brain-homeobox 2 (Gbx2) in NC cell migration and positioning of motor neurons in the developing hindbrain. In addition, loss of Gbx2 function studies in mutant mouse embryos, Gbx2neo, demonstrate a requirement for Gbx2 for the development of NC-derived sensory neurons and axons constituting the mandibular branch of the trigeminal nerve (CNV). Our recent GBX2 target gene identification study identified multiple genes required for the migration and survival of NC cells (e.g., Robo1, Slit3, Nrp1). In this report, we performed loss-of-function analyses using Gbx2neo mutant embryos, to improve our understanding of the molecular and genetic mechanisms regulated by Gbx2 during anterior hindbrain and CNV development. Analysis of Tbx20 expression in the hindbrain of Gbx2neo homozygotes revealed a severely truncated rhombomere (r)2. Our data also provide evidence demonstrating a requirement for Gbx2 in the temporal regulation of Krox20 expression in r3. Lastly, we show that Gbx2 is required for the expression of Nrp1 in a subpopulation of trigeminal NC cells, and correct migration and survival of cranial NC cells that populate the trigeminal ganglion. Taken together, these findings provide additional insight into molecular and genetic mechanisms regulated by Gbx2 that underlie NC migration, trigeminal ganglion assembly, and, more broadly, anterior hindbrain development.
Highlights
The wide range of phenotypes reported in gastrulation-brain-homeobox 2 (Gbx2) mutant organisms suggest that Gbx2 contributes to numerous divergent cell types and their derivatives during development [1,2,3,4]
Given the severity of anterior hindbrain defects observed in Gbx2−/− mouse, we utilized Gbx2neo/neo mice to investigate the motor neuron and neural crest (NC) cell populations that populate nV
Analysis of Gbx2neo/neo mice at P0 revealed that they are born with normal Mendelian frequency [2]
Summary
The wide range of phenotypes reported in Gbx mutant organisms suggest that Gbx contributes to numerous divergent cell types and their derivatives during development [1,2,3,4]. The highly motile cranial neural crest (NC) cells are one such cell type that Gbx is thought to regulate during vertebrate development [5,6]. Multipotent cranial NC cells delaminate and migrate ventrolaterally from the dorsal neuroepithelium, forming components of the cranial ganglion and craniofacial skeletal structures in the distal branchial arches [7]. Cranial NC cells from the midbrain will innervate the distal region of branchial arch (BA) and give rise to components of the upper jaw bones and cartilage, while the anterior hindbrain cranial NC cell populations innervate the proximal region to form elements of the lower jaw [8].
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