title: Regulation of self-renewing neural progenitors by FGF/ERK signaling controls formation of the inferior colliculus.
abstract: The embryonic tectum displays an anteroposterior gradient in development and produces the superior colliculus and inferior colliculus. Studies suggest that partition of the tectum is controlled by different strengths and durations of FGF signals originated from the so-called isthmic organizer at the mid/hindbrain junction; however, the underlying mechanism is unclear. We show that deleting Ptpn11, which links FGF with the ERK pathway, prevents inferior colliculus formation by depleting a previously uncharacterized stem cell zone. The stem-zone loss is attributed to shortening of S phase and acceleration of cell cycle exit and neurogenesis. Expression of a constitutively active Mek1 (Mek1DD), the known ERK activator, restores the tectal stem zone and the inferior colliculus without Ptpn11. By contrast, Mek1DDexpression fails to rescue the tectal stem zone and the inferior colliculus in the absence of Fgf8 and the isthmic organizer, indicating that FGF and Mek1DDinitiate qualitatively and/or quantitatively distinctive signaling. Together, our data show that the formation of the inferior colliculus relies on the provision of new cells from the tectal stem zone. Furthermore, distinctive ERK signaling mediates Fgf8 in the control of cell survival, tissue polarity and cytogenetic gradient during the development of the tectum.
authors: Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-6403, USA.
authors: Alexander
authors: A
authors: Dee
authors: Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-6403, USA.
authors: Kairong
authors: K
authors: Li
authors: Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-6403, USA.
authors: Xin
authors: X
authors: Heng
authors: Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-6403, USA.
authors: Qiuxia
authors: Q
authors: Guo
authors: Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-6403, USA jali@uchc.edu.|Institute for Systems Genomics, School of Medicine, University of Connecticut Health, Farmington, CT 06030, USA.
authors: James Y H
authors: 0000-0002-9231-2698
authors: JY
authors: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001369:Axons / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D007245:Inferior Colliculi / Q000166:cytology* / Q000378:metabolism*; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism; D018345:Mice, Knockout; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: C496457:Fgf8 protein, mouse; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; C516725:Ptpn11 protein, mouse
keywords: ERK signaling pathway; FGF; Mouse; Neural progenitor; Organizer; Ptpn11; Shp2; Stem cells