Development 129, 761-773 (2002) 761 Printed in Great Britain © The Company of Biologists Limited 2002 DEV9814 Patterning of the basal telencephalon and hypothalamus is essential for guidance of cortical projections Oscar Marín1, Joshua Baker1, Luis Puelles2 and John L. R. Rubenstein1 1Department of Psychiatry, Nina Ireland Laboratory of Developmental Neurobiology, Langley Porter Psychiatric Institute, University of California, San Francisco, USA 2Departament of Morphological Sciences, School of Medicine, University of Murcia, Spain *Author for correspondence (e-mail:
[email protected]) Accepted 1 November 2001 SUMMARY We have investigated the mechanisms that control the corticothalamic or thalamocortical axons. In vitro guidance of corticofugal projections as they extend along experiments demonstrate that the basal telencephalon and different subdivisions of the forebrain. To this aim, we the hypothalamus contain an activity that repels the growth analyzed the development of cortical projections in mice of cortical axons, suggesting that loss of this activity is that lack Nkx2-1, a homeobox gene whose expression is the cause of the defects observed in Nkx2-1 mutants. restricted to two domains within the forebrain: the Furthermore, analysis of the expression of candidate basal telencephalon and the hypothalamus. Molecular molecules in the basal telencephalon and hypothalamus of respecification of the basal telencephalon and Nkx2-1 mutants suggests that Slit2 contributes to this hypothalamus in Nkx2-1-deficient mice causes a severe activity. defect in the guidance of layer 5 cortical projections and ascending fibers of the cerebral peduncle. These axon tracts Key words: Nkx2-1, Axon guidance, Transcription factor, Patterning, take an abnormal path when coursing through both Telencephalon, Cortex, Corticofugal projection, Corticothalamic the basal telencephalon and hypothalamus.