Global Constraints within the Developmental Program of theDrosophilaWing

Abstract

Organismal phenotypes emerge from a complex set of genotypic interactions. While technological advances in sequencing provide a quantitative description of an organism's genotype, characterization of an organism's physical phenotype lags far behind. Here, we relate genotype to the complex and multi-dimensional phenotype of an anatomical structure using the Drosophila wing as a model system. We develop a mathematical approach that enables a robust description of biologically salient phenotypic variation. Analysing natural phenotypic variation, and variation generated by weak perturbations in genetic and environmental conditions during development, we observe a highly constrained set of wing phenotypes. In a striking example of dimensionality reduction, the nature of varieties produced by the Drosophila developmental program is constrained to a single integrated mode of variation in the wing. Our strategy demonstrates the emergent simplicity manifest in the genotype-to-phenotype map in the Drosophila wing and may represent a general approach for interrogating a variety of genotype-phenotype relationships.

MAPPER: A new image analysis pipeline unmasks differential regulation ofDrosophilawing features

“…For example, the WINGMACHINE pipeline requires a specific wing orientation for extraction of landmark positions. Recent work assessing wing phenotypes used an open source ML-based pixel classifier ILASTIK (Sommer et al 2011) for the task of segmenting the overall wing blade (Alba et al 2020). To date, there is not a fully automated and high throughput image analysis pipeline that can be used for processing a broad range of phenotypes.…”

“…Adding to this, some pipelines require the wing to be imaged in a specific orientation for estimation of landmark features, further increasing the processing time involved in reorienting images. Recent work has proposed rotation-free estimation of landmark coordinates (Alba et al 2020). However, this approach does not quantify local variations in patterning of the peripheral shape of the wing.…”

An ensemble approach to the structure-function problem in microbial communities

“…Specifically, from proteins (Halabi et al, 2009) to multicellular organisms (Alba et al, 2021), examining statistical variation across many replicates of a system, or an ensemble, has proven powerful. For example, covariation across ensembles of homologous proteins have been used to reveal which amino acids are in contact in the folded structure (Russ et al, 2005), and co-evolving groups of residues that correlate with enzyme function (Halabi et al, 2009).…”

“…Statistical analysis of morphological variation across higher organisms suggests that morphologies adhere to constraints that some believe are associated with specific functional capabilities (Raup and Michelson, 1965;Shoval et al, 2012). A recent study of variation in patterning in the fly wing shows that a single mode of variation describes the response of the wing developmental program to genetic and environmental perturbations (Alba et al, 2021). For a recent piece discussing why low-dimensionality might be an inherent property of evolved systems, see Eckmann and Tlusty (2021).…”