High copy arrays containing a sequence upstream of mec-3 alter cell migration and axonal morphology in C. elegans

BACKGROUND: The Caenorhabditis elegans gene mec-3 encodes a LIM-homeodomain protein that is a master regulator of touch receptor neuron genes. Two of the touch neurons, the ALM neurons, are generated in the anterior of the animal and then migrate to near the middle of the animal. In animals transformed with a sequence upstream of mec-3, the ALM touch receptor neurons failed to migrate to their normal positions and sometimes migrated in the wrong direction, and the PLM touch receptor neurons showed axonal defects. Here we characterize this effect and identify the sequence causing the cell migration and axonal defects. RESULTS: The ALM migration defect did not result from RNA interference (RNAi), nonspecific effects of carrying a transgenic array, expression of GFP, or the marker gene used to make the transformants. Instead, the ALM migration defect resulted from transgenic arrays containing many copies of a specific 104 bp DNA sequence. Transgenic arrays containing this sequence did not affect all cell migrations. CONCLUSIONS: The mec-3 upstream sequence appeared to be sequestering (titrating out) a specific DNA-binding factor that is required for the ALMs to migrate correctly. Because titration of this factor could reverse the direction of ALM migrations, it may be part of a program that specifies both the direction and extent of ALM migrations. mec-3 is a master regulator of touch receptor neuron genes, so the factor or factors that bind this sequence may also be involved in specifying the fate of touch receptor neurons

The Transition to Motherhood: Childbearing and Subsequent Body Mass Index

The purpose of this research is: 1) to advance our understanding of the impact early childbearing may have on becoming obese among US women; and 2) to determine if earlier age at first birth among minority women may contribute to their higher prevalence of obesity relative to white women. Analyses are conducted with data from the Panel Study of Income Dynamics (PSID). There are three specific aims: 1: Describe how allostatic load provides a framework to understand the contributions of reproductive events to body mass index (BMI) over the life course. 2: Determine the impact of the transition to motherhood on BMI. 3: Determine if the association between the transition to motherhood and subsequent BMI differs by age at first birth and minority status. Chapter three completes specific aim one by presenting the conceptual basis for the pathways connecting childbearing, obesity and stress. It describes the manner in which these linkages may contribute to obesity disparities among women in the US. Chapter four completed specific aim two. It examines the association of the transition to motherhood with a woman’s BMI. Evidence supports a relation between parity and an increase in BMI (p<0.004, 95%CI: 0.23, 1.12). Chapter five completes specific aim three by examining associations of obesity with age at first birth and minority status. Results suggest that for each year beyond age 15 that a woman’s first birth is delayed, BMI decreases by 0.20 units (p<0.001; 95%CI: -0.34, -0.06). Age at first birth was most strongly associated with BMI among the youngest group of women. Women who experienced their first birth at 21 years or younger had a BMI five units greater than women who delayed childbearing until at least 30 years (5.02; p=0.02, 95%CI: 0.65, 9.40). Evidence from these analyses support a positive association between childbearing and increasing BMI. Findings suggest the most substantial impact occurs with the first birth and among women who experience the transition to motherhood at 21 years or younger