Lim1 transcription factor

Lim-1 is a homeobox transcription factor. This transcription factor is found in adults in the cerebellum, kidneys, and cerebrum, but plays a larger role in development of the fetal head and the female reproductive tract during gestation. During development it is found in the anterior visceral endoderm, is in tissues formed by the primitive streak, and is required in both tissues for head formation. Lim1 is a member of the LIM homeobox gene and encodes a 406 amino acid protein.

Effects on formation of the future head

In mice, Lim-1 acts in the early development of the mesoderm and ectoderm layers of the developing embryo. The factor is induced by the increasing concentrations of Cerebrus, DKK1, and Nodal around day 7–9 in the mouse embryo. Lim-1 contributes to the formation of the anterior portion of the developing head containing the forebrain and midbrain. Research studies have shown that knocking out Lim-1 in mice will cause a range of head deformities, including the complete lack of formation of the head.

Effects on formation of the female reproductive tract

Lim-1 is also essential for the development of the female reproductive tract, as it causes the persistence of the mullerian ducts that will eventually develop into the oviducts, uterus, cervix, and vagina. Without the expression of Lim-1, formation of the epithelial and mesenchymal cells of the reproductive tract will not occur. While the ovaries will develop, female mice will develop without a uterus and oviducts.

Ssdp1 Regulation On Lim-1

Lim-1 is a transcription factor we have learned about in class to control head and limb development. In our lecture, we learned that the primitive node will secrete the signaling molecules “Lefty” and “Cerebus” that then induce the expression of Lim-1, which will then induce formation of head structures. In one research article, “headshrinker mutants”, were also defined by the Ssdp1 gene being disrupted, which also seemed to be associated with defects in the head induction process. It turns out that this data showed Ssdp1 causing “defects in prechordal plate development and anterior truncations.” This data also discloses that Ssdp1 is a coactivator that enhances transcriptional activity with Lim-1 as a complex. These phenotypes expressed by Ssdp1 mutants most likely reflect reduced activity of a Lim-1 complex. So, while Lim-1 acts as the transcription factor heavily responsible for head development, there are many other factors that affect expression of the normal head phenotype.

In mice

Lim1 is down regulated after embryonic day 7.5. Then, the Lim1 gene, with help from the anterior definitive mesoderm, goes to regulate sequential signaling from the anterior visceral endoderm. This signal regulation is necessary for head formation. The Lim1 gene is also expressed in adult life, possibly to maintain a differentiated state in neural tissue of adults. During embryogenesis, Lim1 is expressed from the central nervous system (CNS) and the excretory system (primarily the kidney). In the CNS, it is expressed approximately 10 days after fertilization and patterns the forebrain, midbrain, hindbrain, and spinal cord regions. In the spinal cord Lim1 is expressed in dorsal and lateral parts but is not detected in the ventricular region.