Math1 expression redefines the rhombic lip derivatives and reveals novel lineages within the brainstem and cerebellum.
The rhombic lip (RL) is an embryonic proliferative neuroepithelium that generates several groups of hindbrain neurons. However, the precise boundaries and derivatives of the RL have never been genetically identified. We use beta-galactosidase expressed from the Math1 locus in Math1-heterozygous and Math1-null mice to track RL-derived cells and to evaluate their developmental requirements for Math1. We uncover a Math1-dependent rostral rhombic-lip migratory stream (RLS) that generates some neurons of the parabrachial, lateral lemniscal, and deep cerebellar nuclei, in addition to cerebellar granule neurons. A more caudal Math1-dependent cochlear extramural stream (CES) generates the ventral cochlear nucleus and cochlear granule neurons. Similarly, mossy-fiber precerebellar nuclei require Math1, whereas the inferior olive and locus coeruleus do not. We propose that Math1 expression delimits the extent of the rhombic lip and is required for the generation of the hindbrain superficial migratory streams, all of which contribute neurons to the proprioceptive/vestibular/auditory sensory network.
Wang
Vincent Y
VY
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Rose
Matthew F
MF
Zoghbi
Huda Y
HY
D000367:Age Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D001933:Brain Stem / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D003051:Cochlea / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006026:Glycoside Hydrolases / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D060850:LIM-Homeodomain Proteins; D007763:Lac Operon / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009474:Neurons / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D020825:T-Box Domain Proteins; D014157:Transcription Factors
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D006026:Glycoside Hydrolases; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D014157:Transcription Factors; C500943:Atoh1 protein, mouse; C117058:Lhx9 protein, mouse; C492271:Tbr1 protein, mouse; C089138:beta-galactanase