Rostral-caudal distribution of Emx1-lineage stem/transit amplifying cells and lineage progression in embryonic cortex depend on Hedgehog signaling.
Lineage progression of neural precursors to an EGF-responsive state can be promoted by several extrinsic signals, including fibroblast growth factor 2 (FGF2) and Hedgehog (Hh). It has been suggested that EGF-responsive precursors in the embryonic cerebral cortex originate in the ventral telencephalon in an FGF-dependent manner and migrate dorsally. To determine whether cortical EGF-responsive cells originate locally from dorsal precursors, we marked these precursors using Emx1-cre and the cre reporter Z/EG and observed a local origin for EGF-responsive cells. We also found a rostral-caudal difference in the abundance of self-renewing, neurogenic Emx1-lineage precursors, with more present rostrally. Deleting the Hh receptor smoothened in Emx-1 lineage cells impaired their progression to an EGF-responsive state. Moreover, loss of smoothened increased the proportion of neurogenic, self-renewing Emx1-lineage cells in caudal regions of cortex, eliminating their asymmetric distribution. Our results support the idea that Hh signaling promotes lineage progression of stem/transit amplifying cells, particularly in caudal regions of the embryonic cortex, leading to rostral-caudal differences in the abundance of neurogenic, self-renewing precursors.
Department of Neurobiology, University of Pittsburgh School of Medicine, W1454 Biomedical Science Tower, Pittsburgh, Pennsylvania, 15261.
Laura
L
Lillien
D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology; D004622:Embryo, Mammalian; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099260:Empty Spiracles Homeobox Proteins
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D049452:Green Fluorescent Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D018809:Proliferating Cell Nuclear Antigen; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C491022:Smo protein, mouse; C541485:EGFR protein, mouse
EGF receptor; cerebral cortex; smoothened