Biomedical subjects

Diana J Laird

Publications and source records attributed to Diana J Laird.

5 recordsLinked to original sources

PubMed2025

Evaluating Selective Quality Control in Mammalian Oogenesis: Evidence and Opportunities.

The formation and maintenance of the finite mammalian ovarian reserve are critical for fertility and species survival. Genetic and developmental studies have uncovered various mechanisms underlying oocyte development and maturation, revealing two curious features of the ovarian germline: (a) The establishment of the follicle reserve involves an initial massive overproduction of oocyte precursors, and (b) the total number of ovulated oocytes across an animal's fertile lifetime is a very small proportion of the initial ovarian reserve. Many have proposed that this indicates the existence of selective quality control to ensure gamete fitness. Here, we review the findings underlying the hypotheses for germline quality control during prepubertal development, homeostatic fertility, and reproductive aging. We evaluate whether the existing evidence base distinguishes the active selection of specific germ cell subsets from neutral dynamics. Throughout, we discuss strategies for applying statistical frameworks to evaluate selection in oogenesis and the implications of neutrality versus selection at various points in oocyte development.

Oogenesis↗

PubMed2005

Stem cells are units of natural selection in a colonial ascidian.

Stem cells are highly conserved biological units of development and regeneration. Here we formally demonstrate that stem cell lineages are also legitimate units of natural selection. In a colonial ascidian, Botryllus schlosseri, vascular fusion between genetically distinct individuals results in cellular parasitism of somatic tissues, gametes, or both. We show that genetic hierarchies of somatic and gametic parasitism following fusion can be replicated by transplanting cells between colonies. We prospectively isolate a population of multipotent, self-renewing stem cells that retain their competitive phenotype upon transplantation. Their single-cell contribution to either somatic or germline fates, but not to both, is consistent with separate lineages of somatic and germline stem cells or pluripotent stem cells that differentiate according to the niche in which they land. Since fusion is restricted to individuals that share a fusion/histocompatibility allele, these data suggest that histocompatibility genes in Botryllus evolved to protect the body from parasitic stem cells usurping asexual or sexual inheritance.

Animals↗

PubMed2005

Identification of a novel gene involved in asexual organogenesis in the budding ascidian Botryllus schlosseri.

Development via regeneration or budding shares some known genetic pathways with embryogenesis, but no concerted effort has been made to identify genes unique to asexual development. We have identified a novel gene that plays a role in cyclical bud formation and asexual organogenesis in the colonial ascidian Botryllus schlosseri. Athena mRNA is transcribed at high levels during the 24- to 36-hr interval of programmed cell death and new bud initiation at the conclusion of the budding cycle (takeover). Knockdown of Athena by RNAi and antisense morpholinos induced defects in the development of new buds ranging from retardation in growth and abnormal organogenesis to hollow buds lacking organs. As genetic intervention in this organism has not been possible, this study establishes the use of RNAi and morpholinos in Botryllus as well as describing the knockdown phenotype of a new gene.

Amino Acid Sequence↗

PubMed2004

Telomerase maintained in self-renewing tissues during serial regeneration of the urochordate Botryllus schlosseri.

Telomerase is critical for the protection of germ line and stem cell chromosomes from fatal shortening during replication. In most organisms, telomerase activity is suppressed in progressively committed cells and falls to basal rates in terminally differentiated lineages. The colonial ascidian Botryllus schlosseri propagates asexually and sexually, presumably from pools of stem cells that self-renew throughout the 2- to 5-year colony life span. Asexual budding takes place continuously from the parental body wall. When the colony reaches a critical size, sexual reproduction commences with the generation of gonads. Here, we establish the existence of 6-15 kb telomeres on the ends of Botryllus chromosomes. We develop a real-time quantitative PCR telomeric repeat amplification protocol (TRAP) assay that reliably detects 0.2-100 TPG units in cells and tissues. We find highest levels of enzymatic activity in the gonads, developing embryos, and tissues containing the earliest asexual buds. Telomerase activity appears to be suppressed in later buds during organogenesis and falls to basal rates in mature zooids. We postulate that this pattern reflects maximum telomere restoration in somatic stem cells of early buds and suppression of telomerase activity in progenitors and terminally differentiated cells, indicative of an alternate role for stem cells as repeated body regenerators in colonial life histories.

Animals↗

PubMed2004

Continuous development precludes radioprotection in a colonial ascidian.

Colonial organisms provide a unique experimental system for stem cell biology. The colonial Urochordate Botryllus schlosseri reproduces sexually as well as by continuous asexual budding. Adjacent colonies with a shared histocompatibility allele undergo vascular fusion and establish a common blood circulation, performing natural transplantation. Fused colonies become chimeras, often with complete somatic replacement of the host cell genotype by the fused parabiont. We attempted to establish a radioprotection assay for the somatic stem cells that induce long-term chimerism in Botryllus. We demonstrate over a range of radiation doses that neither autologous nor allogeneic cell transplantation enhances survival of host colonies. This suggests that high mitotic index associated with continuous asexual development leads to radiosensitivity of organs and structures essential to survival during engraftment. We observe that radiation induces uncontrolled epithelial cell proliferation in abnormally terminated buds, suggesting that stem cells are not required for the initial stages of bud development.

Animals↗