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The role of Dlx homeogenes in early development of the olfactory pathway

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An Erratum to this article was published on 11 December 2007

Abstract

Development of the olfactory pathway requires interaction between cells and signals of different origin. Olfactory receptor neurons (ORN) in the olfactory placodes (OP) extend axons towards the forebrain (FB); with innervation taking place at a later time following degradation of the basement membrane. Cells from the OP migrate along ORN axons and differentiate into various elements, including ensheathing and Gonadotropin Releasing Hormone (GnRH)+ cells. The importance of the olfactory connection and migration is highlighted by the severe endocrine phenotype in Kallmann’s patients who lack this migratory pathway. Little is known about the genetic control of intrinsic ORN properties. Inactivation of the distalless-related Dlx5 prevents connections between ORNs and FB. Using a grafting approach we show that misguidance and lack of connectivity is due to intrinsic defects in ORN neurites and migratory cells (MgC), and not to environmental factors. These data point to a cell-autonomous function of Dlx5 in providing ORN axons with their connectivity properties. Dlx5 also marks a population of early MgC that partly overlaps with the GnRH+ population. In the absence of Dlx5 MgCs of the Dlx5+ lineage migrate, associated with PSA-NCAM+ axons, but fail to reach the FB as a consequence of the lack of axonal connection and not an inability to migrate. These data suggests that Dlx5 is not required to initiate migration and differentiation of MgCs.

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Acknowledgements

We thank Drs. Stefano Bertuzzi (NINDS, Bethesda, USA), Robert Benoit (McGill University, Montreal, Canada) and Thomas Sargent (NICHD Bethesda, USA) for probes and reagents. We are grateful to Dr. Adam Puche (Univ. Maryland, Baltimore, USA) for helpful comments on the manuscript. G.R.M. is recipient of a Telethon Career Award (TCP99003), is supported by Cariplo (2004–2005) and SanPaolo (2006 DTI). P.P. is supported by Compagnia SanPaolo (Neurotransplant). A.A.Z is in the Doctorate Program of the University of Milano.

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Authors and Affiliations

  1. Dulbecco Telethon Institute, CNR-ITB Milano, Via F.lli Cervi 93, 20090, Segrate, Milano, Italy

    Giorgio R. Merlo, Stefano Mantero, Ambra A. Zaghetto, Sara Paina & Marianna Gozzo

  2. Department of Biology, Comparative Anatomy Section, University of Milano, Milano, Italy

    Ambra A. Zaghetto

  3. Department of Animal and Human Biology, University of Torino, Turin, Italy

    Paolo Peretto

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  1. Giorgio R. Merlo
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  2. Stefano Mantero
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Correspondence to Giorgio R. Merlo.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s10735-007-9154-x

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Merlo, G.R., Mantero, S., Zaghetto, A.A. et al. The role of Dlx homeogenes in early development of the olfactory pathway. J Mol Hist 38, 347–358 (2007). https://doi.org/10.1007/s10735-007-9109-2

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