title: Transit amplification in the amniote cerebellum evolved via a heterochronic shift in NeuroD1 expression.
abstract: The cerebellum has evolved elaborate foliation in the amniote lineage as a consequence of extensive Atoh1-mediated transit amplification in an external germinal layer (EGL) comprising granule cell precursors. To explore the evolutionary origin of this layer, we have examined the molecular geography of cerebellar development throughout the life cycle of Xenopus laevis. At metamorphic stages Xenopus displays a superficial granule cell layer that is not proliferative and expresses both Atoh1 and NeuroD1, a marker of postmitotic cerebellar granule cells. Premature misexpression of NeuroD1 in chick partially recapitulates the amphibian condition by suppressing transit amplification. However, unlike in the amphibian, granule cells fail to enter the EGL. Furthermore, misexpression of NeuroD1 once the EGL is established both triggers radial migration and downregulates Atoh1. These results show that the evolution of transit amplification in the EGL required adaptation of NeuroD1, both in the timing of its expression and in its regulatory function, with respect to Atoh1.
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, 4th Floor New Hunt's House, London SE1 1UKL, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Butts
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, 4th Floor New Hunt's House, London SE1 1UKL, UK.
authors.forename: Michalina
authors.initials: M
authors.lastname: Hanzel
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, 4th Floor New Hunt's House, London SE1 1UKL, UK richard.wingate@kcl.ac.uk.
authors.forename: Richard J T
authors.initials: RJ
authors.lastname: Wingate
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D005075:Biological Evolution; D002465:Cell Movement; D049109:Cell Proliferation; D002531:Cerebellum / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D002642:Chick Embryo; D002645:Chickens; D017124:Conserved Sequence; D008018:Life Cycle Stages; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; C093564:Neurogenic differentiation factor 1
keywords: Atoh1; Cerebellum; Chick; Evolution; Xenopus