Cell development and determination

During the development of an embryo, how is the function of a cell determined? How does a cell “know” it is supposed to, for example, become a nerve cell or part of the gut? How does it know its location within the embryo? How does the process happen?

Key articles about cell development and cell determination:

*Kemphues, K. J., Priess, J. R., Morton, D. G., & Cheng, N. S. (1988). Identification of genes required for cytoplasmic localization in early C. elegans embryos. Cell, 52(3), 311-320. [PDF] [Cited by]

“We have isolated and analyzed eight strict maternal effect mutations identifying four genes, par-1, par-2, par-3, and par-4, required for cytoplasmic localization in early embryos of the nematode C. elegans. Mutations in these genes lead to defects in cleavage patterns, timing of cleavages, and localization of germ line-specific P granules. Four mutations in par-1 and par-4 are fully expressed maternal effect lethal mutations; all embryos from mothers homozygous for these mutations arrest as amorphous masses of differentiated cells but are specifically lacking intestinal cells. Four mutations in par-2, par-3, and par-4 are incompletely expressed maternal effect lethal mutations and are also grandchildless; some embryos from homozygous mothers survive and grow to become infertile adults due to absence of functional germ cells. We propose that all of these defects result from the failure of a maternally encoded system for intracellular localization in early embryos.”

*Lesch, B. J., & Page, D. C. (2012). Genetics of germ cell development. Nature Reviews.Genetics, 13(11), 781-794. [PDF] [Cited by]

“The germ line represents a continuous cellular link between generations and between species, but the germ cells themselves develop in a specialized, organism-specific context. The model organisms Caenorhabditis elegans, Drosophila melanogaster and the mouse display striking similarities, as well as major differences, in the means by which they control germ cell development. Recent developments in genetic technologies allow a more detailed comparison of the germ cells of these three organisms than has previously been possible, shedding light not only on universal aspects of germline regulation, but also on the control of the pluripotent state in vivo and on the earliest steps of embryogenesis. Here, we highlight themes from the comparison of these three alternative strategies for navigating the fundamental cycle of sexual reproduction.

  • Germ cells are specialized cells that are responsible for transmitting the genome of an individual organism to its offspring.
  • The defining characteristic of the germ cells is their ability to undergo meiosis, in which the diploid genome is reduced to a haploid genome that can combine with another haploid genome at fertilization.
  • Many of the factors specifying germ cell identity are RNA-binding factors, and many of these RNA-binding factors are conserved in the germ cells across multiple species.
  • Maintenance of a transcriptionally repressed state is a characteristic of early germ cells in multiple species. Repression is accomplished both by the direct inhibition of RNA polymerase II and by the establishment of a repressive chromatin configuration.
  • The decision to stop mitotic proliferation and to enter meiosis is timed differently in the different species and in different sexes of the same species. In some cases, a proliferative pool of germline precursors is retained after this decision, and in some cases all available germ cells enter meiosis together.
  • The later steps of germ cell development set up the cues that will guide the earliest stages of embryogenesis.
  • Germ cells represent the closest in vivo equivalent to in vitro pluripotent stem cell systems; understanding germ cell biology will provide new insights into the nature of pluripotency.”

*Priess, J. R., Schnabel, H., & Schnabel, R. (1987). The glp-1 locus and cellular interactions in early C. elegans embryos. Cell, 51(4), 601-611. [Cited by]

“Interactions between the early blastomeres in a C. elegans embryo are required for the specification of certain cell fates. Blastomeres that produce neurons and skin cells when cultured in isolation are induced to also produce pharyngeal cells in intact embryos. We have identified maternal effect lethal mutations that, on the basis of phenotype and temperature-sensitive period, appear to disrupt this inductive interaction. These mutations are all alleles of glp-1, a gene also involved in the control of germ cell proliferation during postembryonic development of C. elegans.”

*Priess, J. R., & Thomson, J. N. (1987). Cellular interactions in early C. elegans embryos. Cell, 48(2), 241-250. [Cited by]

“In normal development both the anterior and posterior blastomeres in a 2-cell C. elegans embryo produce some descendants that become muscles. We show that cellular interactions appear to be necessary in order for the anterior blastomere to produce these muscles. The anterior blastomere does not produce any muscle descendants after either the posterior blastomere or one of the daughters of the posterior blastomere is removed from the egg. Moreover, we demonstrate that a daughter of the anterior blastomere that normally does not produce muscles appears capable of generating muscles when interchanged with its sister, a cell that normally does produce muscles. Embryos develop normally after these blastomeres are interchanged, suggesting that cellular interactions play a major role in determining the fates of some cells in early embryogenesis.”

*Tintori, S. C., Osborne Nishimura, E., Golden, P., Lieb, J. D., & Goldstein, B. (2016). A Transcriptional Lineage of the Early C. elegans Embryo. Developmental Cell, 38(4), 430-444. [PDF] [Cited by]

“During embryonic development, cells must establish fates, morphologies, and behaviors in coordination with one another to form a functional body. A prevalent hypothesis for how this coordination is achieved is that each cell’s fate and behavior is determined by a defined mixture of RNAs. Only recently has it become possible to measure the full suite of transcripts in a single cell. Here we quantify genome-wide mRNA abundance in each cell of the Caenorhabditis elegans embryo up to the 16-cell stage. We describe spatially dynamic expression, quantify cell-specific differential activation of the zygotic genome, and identify genes that were previously unappreciated as being critical for development. We present an interactive data visualization tool that allows broad access to our dataset. This genome-wide single-cell map of mRNA abundance, alongside the well-studied life history and fate of each cell, describes at a cellular resolution the mRNA landscape that guides development.”

See also —

Caenorhabditis elegans: a model organism in Biology

Questions? Please let me know (engelk@grinnell.edu).

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