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Orchestrating ontogenesis: variations on a theme by sonic hedgehog

Nature Reviews Genetics volume 7, pages 841–850 (2006)Cite this article

Key Points

  • Embryonic development is an emergent process in which increasing complexity is generated by sequential cellular interactions that are mediated by members of just a few families of signalling molecules, including the hedgehog (HH) protein family.

  • During their development, embryos undergo extensive proliferation, thereby generating pools of progenitor cells; cells must exit these pools at the appropriate times and places to differentiate into the arrays of specific cell types that characterize different organs.

  • Studies of SHH function in a number of organisms have shown that this secreted signal has important roles in both the control of proliferation and cell-fate specification.

  • In some instances, sonic hedgehog (SHH) functions as a classical morphogen, with the distance of a responding cell from the source of the SHH signal being of crucial importance to its specification; in others cases, it is the duration of exposure to the signal that is the main determinant of cell fate.

  • Cells can move into or out of range of the SHH signal as development proceeds, or can differ in their competence to respond to the signal as a function of either developmental time or location.

  • Many developmental processes integrate inputs from multiple signals. An important challenge that remains in the field is to unravel these complex networks of signalling interactions, and to elucidate the sequences of molecular events that direct cells to do the right thing at the right time and place.

Abstract

Embryonic development is an emergent process in which increasing complexity is generated by sequential cellular interactions. Recently, it has become clear that such interactions are mediated by just a few families of signalling molecules; but how does this limited repertoire elicit the diversity of form that is characteristic of multicellular organisms? Here we review the various ways in which a member of one such family, the sonic hedgehog (SHH) protein, is deployed during embryonic development. These examples of SHH function provide paradigms for inductive interactions that should help to inform attempts to recapitulate cellular programming and organogenesis in vitro.

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Figure 1: Signals can specify cell fate in different ways.
Figure 2: SHH governs cell proliferation, survival and fate in the neural tube.
Figure 3: Specification of muscle cell identity in the zebrafish embryo by Shh.
Figure 4: Control of identity and growth by SHH in the developing vertebrate limb.
Figure 5: Spatial variation in competence to respond to SHH signals underlies the patterning of Drosophila segments and the vertebrate brain.

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Acknowledgements

We thank B. Chia for his hospitality to P.W.I. during his visiting Professorship at Temasek Life Science Laboratory, Singapore. We thank A. Furley for help with figures.

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  1. Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, 138673, Singapore

    Philip W. Ingham

  2. MRC Centre Development for Developmental and Biomedical Genetics, University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN, UK

    Philip W. Ingham & Marysia Placzek

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Glossary

Glia

A non-neuronal cell in the CNS. The three types of glia are astrocytes, oligodendrocytes and microglia.

Multipass-transmembrane protein

An integral membrane protein that spans the membrane more than once and has multiple internal sequences.

Serpentine protein

A protein that spans the membrane seven times.

Interneuron

A neuron that connects with and transmits information only to other neurons.

Cerebellum

The part of the vertebrate hindbrain that modulates the force and range of movements, maintains balance and is involved in motor learning.

Neocortex

The most recently evolved part of the cerebral cortex. It is believed to orchestrate high-level motor, sensory and cognitive functions.

Tectum

The dorsal portion of the midbrain (mesencephalon) that mediates reflexive responses to visual and auditory stimuli.

Myotome

Tissue formed from somites that develops into the body wall muscle.

Presomitic mesoderm

Precursor unsegmented mesoderm, which generates somites on segmentation.

Motor neuron

A nerve cell that innervates muscle cells.

Diencephalon

The region of the brain that includes the thalamus, hypothalamus, epithalamus and subthalamus; derived from the prosencephalon.

Prethalamic primordium

The early developing prethalamus.

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Ingham, P., Placzek, M. Orchestrating ontogenesis: variations on a theme by sonic hedgehog. Nat Rev Genet 7, 841–850 (2006). https://doi.org/10.1038/nrg1969

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