Role of morphogens in brain growth.
During the last century, experiments on the chick embryo established that the ballooning expansion of the early forebrain and midbrain vesicles is dependent on the underlying axial (notochordal) mesoderm. Transient separation of the early midbrain primordium from the notochord causes subsequent collapse of both midbrain and forebrain (telencephalic) vesicles, accompanied by pronounced folding of the neural epithelium. More recent experiments have shown that vesicle collapse is caused by defective Sonic Hedgehog (Shh) signaling from the notochord and floor plate. Separation of the notochord from the brain causes loss of ventral Shh expression, resulting in reduced cell proliferation and increased cell death in the expanding neural epithelium, and culminating in vesicle collapse. These experiments are reviewed here, and set in the context of other studies illustrating the wide range of molecular and cellular processes that cause abnormal brain morphogenesis when perturbed. We also speculate that variation in the regulation of signaling pathways such as Hedgehog may have played a significant part in generating rapid morphogenetic changes during the evolution of the vertebrate brain.
Tannahill
David
D
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.
Harris
Laura W
LW
Keynes
Roger
R
D000818:Animals; D001921:Brain / Q000196:embryology / Q000254:growth & development*; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002555:Cerebrospinal Fluid / Q000502:physiology; D002645:Chickens; D053823:Hedgehog Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology
D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; C509239:SHH protein, human; D015534:Trans-Activators