ScienceWeek

4. GENOME BIOLOGY: ON HETEROCHRONIC GENES

The following points are made by Allison L. Abbott (Current Biology 2003 13:824):

1) In this context, the term "heterochronic" refers to the development of cells or tissues at an abnormal time relative to other unaffected events in an organism; the latter can thus serve as temporal landmarks. Mutations in heterochronic genes cause certain cells to adopt cell fates normally associated with earlier or later times in development. Heterochronic genes therefore regulate the timing and sequence of developmental events in specific cell lineages, and thereby coordinate events throughout a developing organism.

2) The nematode worm Caenorhabditis elegans provides a particularly tractable model for studying heterochronic genes, owing to its relatively simple and invariant cell lineages. In the four larval stages of its post-embryonic development, C. elegans cells exhibit stage-specific patterns of developmental events, such as cell division and cell fate specification, with each stage separated by a molt. Importantly, neither larval growth nor progression through the molting cycle in the worm are affected by known heterochronic mutations, allowing developmental events to be monitored relative to these temporal landmarks.

3) Heterochronic genes have been reported in many different organisms, including Drosophila (hunchback, pdm, castor) and several species of plants, including Arabidopsis (HASTY) and rice (mori1). In C. elegans, one class of heterochronic mutations results in an early, or precocious, phenotype in which many of the normal cell fate decisions of a specific larval stage are skipped and much of the worm instead executes the developmental program of a later stage. Examples include mutations in lin-14, lin-28 and lin-41. Worms with such mutations express adult cell fates when the animal is still sexually immature. Conversely, a second class of mutations results in a delayed, or retarded, phenotype in which many normal cell fate decisions are reiterated in subsequent larval stages. Examples include mutations in lin-4 and lin-29. Worms with such mutations do not express certain adult cell fates, despite being sexually mature.

4) An important regulator of the larval-to-adult transition in worms, let-7, is conserved across diverse phyla, having been identified in flies, sea urchins, humans and many other organisms. In addition, it has recently been demonstrated that the C. elegans heterochronic gene lin-57 is a worm homolog of the Drosophila gene hunchback (hence its new name hbl-1). In the developing central nervous system of flies, hunchback regulates the temporal patterning of cell fate specification for neuroblasts.

References (abridged):

1. Abrahante, J.E., Daul, A.L., Li, M., Volk, M.L., Tennessen, J.M., Miller, E.A., and Rougvie, A.E. (2003). The Caenorhabditis elegans hunchback-like gene lin-57/hbl-1 controls developmental time and is regulated by microRNAs. Dev. Cell 4, 625-637

2. Ambros, V. (2001). microRNAs: tiny regulators with great potential. Cell 107, 823-826

3. Brennecke, J., Hipfner, D.R., Stark, A., Russell, R.B., and Cohen, S.M. (2003). bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113, 25-36

4. Isshiki, T., Pearson, B., Holbrook, S., and Doe, C.Q. (2001). Drosophila neuroblasts sequentially express transcription factors which specify the temporal identity of their neuronal progeny. Cell 106, 511-521

5. Lin, S.Y., Johnson, S.M., Abraham, M., Vella, M.C., Pasquinelli, A., Gamberi, C., Gottlieb, E., and Slack, F.J. (2003). The C. elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microRNA target. Dev. Cell 4, 639-650

Current Biology http://www.current-biology.com

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HETEROCHRONY AND HETEROTOPY: STABILITY AND INNOVATION IN THE EVOLUTION OF FORM.

The following points are made by M.L. Zelditch and W.L. Fink (Paleobiology 1996 22:241):

1) Heterochrony, change in developmental rate and timing, is widely recognized as an agent of evolutionary change. Heterotopy, evolutionary change in spatial patterning of development, is less widely known or understood. Although Ernst Haeckel (1834-1919) coined the term as a complement to heterochrony in 1866, few studies have detected heterotopy or even considered the possibility that it might play a role in morphological evolution.

2) The authors review the roles of heterochrony and heterotopy in evolution and discuss how they can be detected. Heterochrony is of interest in part because it can produce novelties constrained along ancestral ontogenies, and hence result in parallelism between ontogeny and phylogeny. Heterotopy can produce new morphologies along trajectories different from those that generated the forms of ancestors.

3) The authors argue that the study of heterochrony has been bound to an analytical formalism that virtually precludes the recognition of heterotopy, so the authors provide a new framework for the construction of ontogenetic trajectories and illustrate their analysis in a phylogenetic context.

4) The authors suggest that the study of development of form needs tools that capture not only rates of development but the space in which the changes are manifest. The authors suggest the framework outlined by them provides tools applicable to both. When appropriate tools are used and the necessary steps are taken, a more comprehensive interpretation of evolutionary change in development becomes possible. The authors suggest there will be very few cases of change solely in developmental rate and timing or change solely in spatial patterning, since most ontogenies evolve by changes of spatiotemporal pattern.

Paleobiology http://www.paleosoc.org/paleobio.htm

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