From: Michel Kerszberg <[email-masked]>
Date: Wed, 4 May 1994 11:43:42 +0200

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	 A Model for Reading Morphogenetic Gradients: Autocatalysis and
			   Competition at the Gene Level

		   Michel Kerszberg and Jean-Pierre Changeux

		Neurobiologie Mol'eculaire, Institut Pasteur,
	     25, rue du Docteur Roux, F-75724 Paris Cedex 15, France

			       ABSTRACT

The mechanisms by which embryonic structures such as insect segments develop
from the fertilized egg (zygote) are becoming unravelled at the molecular
level. Much of early development depends crucially on substances deposited
in the zygote by mother. Such is the case, for instance, in Drosophila, where
a maternally controlled inhomogeneous distribution of the bicoid protein plays
a major role. How are such morphogenetic gradients read and interpreted in
terms of gene activation/inhibition? We propose a hypothetical model based on
recent findings in the molecular biology of transcription factors, which
control gene activity. The model postulates a morphogen which is itself a
spatially distributed transcription factor M, or which generates a
distribution of such factor. We posit the existence of an additional,
zygotically activated ``vernier" factor V. M and V form all possible dimers
MM, MV and VV. These are differentially translocated to the nuclei, and bind
with various affinities to responsive elements in the region which is
involved in controlling V activity (its promoter), thereby contributing to
activation/inactivation of V transcription. We find four generic regimes.
In order of complexity, they are:
1) MM activates V: the M gradient gives rise to a clear transcriptional
   boundary for V, and to a secondary gradient in the concentration of
   protein V.
2) MV activates V: a sharp boundary in transcription  and distribution
   of V arises.
3) MM and MV compete for binding: a stationary stripe of active V
   transcription is generated.
4) MM and VV are in competition: a stripe of V transcription sweeps the
   embryo, and may stop or dwindle at an intermediate position.
Interpretations of these findings in terms of Drosophila genes such as bicoid,
hunchback and Kruppel are presented.

(PNAS May or June, 1994)

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