Abstract

Pigmentation processes occur from invertebrates to mammals. Owing to the complexity of the pigmentary system, in vivo animal models for pigmentation study are limited. Planarians are capable of regenerating any missing part including the dark-brown pigments, providing a promising model for pigmentation study. However, the molecular mechanism of planarian body pigmentation is poorly understood. We found in an RNA interference screen that a forkhead containing transcription factor, Albino, was required for pigmentation without affecting survival or other regeneration processes. In addition, the body color recovered after termination of Albino double stranded RNA feeding owing to the robust stem cell system. Further expression analysis revealed a spatial and temporal correlation between Albino and pigmentation process. Gene expression arrays revealed that the expression of three tetrapyrrole biosynthesis enzymes, ALAD, ALAS and PBGD, was impaired upon Albino RNA interference. RNA interference of PBGD led to a similar albinism phenotype caused by Albino RNA interference. Moreover, PBGD was specifically expressed in pigment cells and can serve as a pigment cell molecular marker. Our results revealed that Albino controls planarian body color pigmentation dominantly via regulating tetrapyrrole biogenesis. These results identified Albino as the key regulator of the tetrapyrrole-based planarian body pigmentation, suggesting a role of Albino during stem cell-pigment cell fate decision and provided new insights into porphyria pathogenesis.

Highlights

  • Biological pigments provide basic granules to form overall body color of an organism as well as critical compartments for cytochrome within a single cell

  • Planarian body pigment accumulates during juvenile development and regeneration Newly hatched worms were born colorless and the pigmentation process took place after the hatching, and it took 12 days for a newborn planarian to get pigmented but the eye spots were pigmented at birth (Supplementary Figure S1A)

  • Tyrosinase, an enzyme critical for melanin biosynthesis, RNA interference (RNAi) led to eyespot pigmentation failure only, rather than body pigment loss (Supplementary Figure S6F). These results revealed that, among the Albino-regulated tetrapyrrole biosynthesis enzymes, porphobilinogen deaminase (PBGD) in particular is required for planarian body color maintenance, suggesting that PBGD serves as the downstream target of Albino in regulating the body pigment of planarian

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Summary

Introduction

Biological pigments provide basic granules to form overall body color of an organism as well as critical compartments for cytochrome within a single cell. A comprehensive understanding of the pigmentation process offers us a theoretical foundation for treatments of pigment-related disorders and especially for stem cell-based regenerative medicine. In this case, an in vivo model for pigmentation study is of great importance. Owing to possessing powerful regenerative abilities, planarian serves as a distinctive model for stem cell and regeneration studies [1, 2]. The Transcription factors have critical roles in guiding the regeneration processes [8, 9]. Vital transcription factors have been identified in planarian polarity establishment [10,11,12,13,14], nerve system [15,16,17], eye [18,19,20], pharynx [21, 22], germline [23,24,25], gut [7, 26]

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